Inhibitors of nitric oxide biosynthesis
The present invention is directed to a new class of compound which are useful as inhibitors of the biosynthesis of nitric oxide.
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Claims
1. A compound of the formula: ##STR9## in which X is represented by cyano, cyclopropyl, 2-propyne, 2, 3-butadiene or NHR.sub.2, in which R.sub.2 is represented by H, or C.sub.1-6 alkyl;
- R is represented by an amino acid or OM in which M is represented by H, C.sub.1-6 alkyl, benzyl, phenyl, or pivoyl methyl ether;
- Z is represented by O or NR.sub.1, in which R.sub.1 is represented by H, --CF.sub.3, --CH.sub.2 CF.sub.3, or C.sub.1-6 alkyl; and
- W is represented by a substituent selected from the group consisting of CH.sub.2 --NH--, --(CH.sub.2).sub.2 --NH--, --NH--NH--, --CH.sub.2 --NH--NH, --CH.sub.2 --O--NH and --O--NH;
- 1) that when W is --NH--NH or --(CH.sub.2).sub.2 --NH-- then Z must be represented by O, and
- 2) that when X is --NHR.sub.2 and Z is --NHR.sub.1 then R.sub.1 and R.sub.2 must t be represented by the same C.sub.1-6 alkyl substituent, and
- 3) that when Z is represented by O and X is represented by NR.sub.1 then W must be --CH.sub.2 --NH-- or --(CH.sub.2).sub.2 --NH--, and
- 4) that when W is represented by CH.sub.2 --NH, Z is represented by NH, and X is NHR.sub.2, then R.sub.2 is not represented by H.
2. A compound according to claim 1 in which X is cyclopropyl.
3. A Compound according to claim 2 in which R is represented by --OM in which M is represented by H, C.sub.1-6 alkyl, benzyl, phenyl, pivoyl methyl ester.
4. A Compound according to claim 3 in which R is represented by --OM where M is represented by H.
5. A Compound according to claim 2 in which R is represented by an amino acid.
6. A Compound according to claim 2 in which Z is represented by NR.sub.1.
7. A Compound according to claim 2 in which Z is represented by O.
8. A compound according to claim 1 in which W is represented by --CH.sub.2 --NH--.
9. A compound according to claim 1 in which Z is NR1 where R1 is H.
10. A Compound according to claim 1 in which X is represented by 2-propyne, or 2,3 butadiene.
11. A pharmaceutical composition comprising a compound according to claim 1 in admixture with a pharmaceutically acceptable carrier.
12. A compound of the formula: ##STR10## in which X is cyclopropyl and
- R is OM, with M represented by H, and
- Z is represented by NR1, with R1 represented by H, and
- W is CH2--NH.
13. A pharmaceutical composition consisting of a compound according to claim 12 in admixture with a pharmaceutically acceptable carrier.
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Type: Grant
Filed: Oct 4, 1994
Date of Patent: Jan 20, 1998
Assignee: Merrell Pharmaceuticals Inc. (Cincinnati, OH)
Inventors: Jeffrey P. Whitten (Cincinnati, OH), Ian A. McDonald (Loveland, OH), Laurie E. Lambert (Morrow, OH), Niall S. Doherty (Lyme, CT)
Primary Examiner: Raymond Henley, III
Assistant Examiner: Keith MacMillan
Attorney: Ruth E. Homan
Application Number: 8/317,458
International Classification: A61K 31195; C07C 6104;
